Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene In­dus­try is grow­ing at a stag­ger­ing 30% CA­GR and is es­ti­mat­ed to reach $14B by 2025¹. A num­ber of cell, gene and stem cell ther­a­py spon­sors cur­rent­ly have nov­el drug sub­stances and prod­ucts and many re­ly on Con­tract De­vel­op­ment Man­u­fac­tur­ing Or­ga­ni­za­tions (CD­MO) to pro­duce them with ad­her­ence to strin­gent reg­u­la­to­ry cGMP con­di­tions. Cell and gene man­u­fac­tur­ing for both au­tol­o­gous (one to one) and al­lo­genic (one to many) treat­ments face dif­fi­cult is­sues such as: a com­plex sup­ply chain, vari­abil­i­ty on pa­tient and cel­lu­lar lev­el, cell ex­pan­sion count and a tight sched­ul­ing of lot dis­po­si­tion process. This com­plex­i­ty af­fects qual­i­ty, com­pli­ance and ac­count­abil­i­ty in the en­tire vein-to-vein process for crit­i­cal­ly ill pa­tients.

Cell and gene com­pa­nies* are emerg­ing from years of lab­o­ra­to­ry scale de­vel­op­ment through pre­clin­i­cal tests and piv­otal clin­i­cal tri­als to ul­ti­mate­ly reach­ing FDA ap­proval and com­mer­cial­iza­tion. Dig­i­tal so­lu­tions such as a ro­bust Elec­tron­ic Batch Record­ing sys­tem (EBR) are vi­tal. Giv­en that the raw ma­te­r­i­al for these process­es are ac­tu­al pa­tient cells ex­tract­ed in a clin­ic; a failed batch is dev­as­tat­ing and could mean the loss of a pa­tient’s life. A failed batch due to poor pa­per record han­dling must be avoid­ed at all costs.

A cru­cial com­po­nent in re­duc­ing Cost of Goods Sold (COGS) in de­vel­op­ing cell, gene and stem cell ther­a­pies is through in­creased ef­fi­cien­cy of the man­u­fac­tur­ing process. Au­toma­tion pro­vides a suit­able op­tion to ad­dress this chal­lenge. Those man­u­fac­tur­ers who have be­come ear­ly adopters of dig­i­ti­za­tion, au­toma­tion and con­tin­u­ous im­prove­ment are reap­ing huge ben­e­fits. They have min­i­mized the use of pa­per, au­tom­a­tized the cal­cu­la­tions, sped the de­sign of man­u­fac­tur­ing batch records, re­duced cGMP de­vi­a­tions and more quick­ly re­leased man­u­fac­tur­ing lots based on re­view by ex­cep­tion, which align with right first time ini­tia­tives.

Cell ther­a­py man­u­fac­tur­ers’ rate man­u­fac­tur­ing process sta­bil­i­ty and scal­a­bil­i­ty as their top two con­sid­er­a­tions through­out clin­i­cal tri­als². They equal­ly rank process vari­abil­i­ty, scale-up ease and re­duced cy­cle time as mo­ti­va­tion for au­tomat­ing both their man­u­fac­tur­ing process­es and sup­ply chain. In this vein, a CD­MO that is al­ready ful­ly au­to­mat­ed fa­cil­i­ty with EBR ca­pa­bil­i­ty can help achieve these goals.

The detri­men­tal im­pact of Sars-Cov-2 has chal­lenged cell ther­a­py spon­sors with a stop­page of clin­i­cal tri­als and sup­ply chain hur­dles. In the man­u­fac­tur­ing do­main, both in-house and con­tract man­u­fac­tur­ers have im­ple­ment­ed strict guide­lines to en­sure em­ploy­ee safe­ty. Man­u­fac­tur­ers, who had em­braced au­toma­tion, quick­ly re­bound­ed to get sys­tems back on­line to meet de­liv­ery dead­lines. In ad­di­tion, they had a re­duced risk of con­t­a­m­i­na­tion as few­er hands touch pa­per or the fi­nal prod­uct, there­by dras­ti­cal­ly re­duc­ing the four-eyes-prin­ci­ple³ steps.

Why Do Cell Ther­a­py Spon­sors Se­lect CD­MOs?

Cell ther­a­py spon­sors have two op­tions for how to man­u­fac­ture. Build an in­ter­nal man­u­fac­tur­ing ca­pa­bil­i­ty or em­ploy a CD­MO/CMO. In­vest­ing in their own man­u­fac­tur­ing fa­cil­i­ty would de­vel­op in­ter­nal ex­per­tise, op­ti­mize process­es, con­trol man­u­fac­tur­ing ca­pac­i­ty, and po­ten­tial­ly save mon­ey in the long run, if the drug com­mer­cial­izes. How­ev­er, uti­liz­ing CD­MOs / CMOs can help pro­vide flex­i­bil­i­ty in ca­pac­i­ty plan­ning, re­duce com­mit­ments to evolv­ing tech­nol­o­gy plat­forms, and re­duce ini­tial in­vest­ments. CD­MOs/CMOs have ex­ist­ing cGMP fa­cil­i­ties de­signed to com­ply with reg­u­la­to­ry au­thor­i­ties.  More im­por­tant­ly, they have a skilled work­force who can ex­e­cute the process, man­u­fac­ture the prod­uct and de­liv­er it to hos­pi­tals and clin­ics.  Some cell ther­a­py spon­sors em­ploy a re­gion­al man­u­fac­tur­ing mod­el and use CD­MOs/CMOs to man­u­fac­ture their prod­ucts in var­i­ous ge­o­graph­i­cal re­gions. Con­cur­rent­ly, small­er-scale spon­sors are uti­liz­ing co-work­ing or col­lab­o­ra­tive spaces such as The Cen­ter for Break­through In­no­va­tion (King of Prus­sia, PA) and Cell and Gene Cat­a­pult (Steve­nage, UK) for meet­ing their de­vel­op­ment and man­u­fac­tur­ing needs.

Spon­sors’ de­mands are grow­ing and com­plex, which have many CD­MOs/CMOs push­ing to be­come lean­er and dig­i­tal. To be ag­ile enough to meet spon­sor re­quire­ments of pa­tient de­liv­ery dead­lines and fre­quent sched­ule changes, an Elec­tron­ic Batch Record so­lu­tion should be a min­i­mum pre­req­ui­site. Pa­per-based man­u­fac­tur­ing sys­tems are too slow and cum­ber­some in the Cell ther­a­py world. They lack the ease for track­ing of da­ta and con­tin­u­ous im­prove­ment.  For in­stance, giv­en the vol­ume of dif­fer­ent man­u­fac­tur­ing process­es in the cell, gene and stem cell space, con­tract man­u­fac­tur­ers must con­tin­u­ous­ly man­age cus­tomers’ work in­struc­tions and stan­dard op­er­at­ing pro­ce­dures (SOPs) which change reg­u­lar­ly. Op­er­a­tor train­ing, man­u­fac­tur­ing recipes and prod­uct spec­i­fi­ca­tions al­so vary and need to be up­dat­ed fre­quent­ly. Ac­cu­rate­ly and safe­ly man­ag­ing all of these chang­ing doc­u­ments via pa­per-based records is in­cred­i­bly chal­leng­ing and in­ef­fi­cient, with sig­nif­i­cant risk for harm­ful er­rors, de­lays and a lack of trans­paren­cy.

In con­clu­sion, CD­MOs/CMOs must em­brace dig­i­ti­za­tion. A cloud-host­ed dig­i­tal elec­tron­ic batch records (EBRs) so­lu­tion cou­pled with a flex­i­ble sched­ul­ing so­lu­tion and in­te­gra­tion to oth­er sup­ply chain and IT sys­tems is the “need of the hour” to­day. With an EBR, cell ther­a­py spon­sors can mon­i­tor the CD­MO/CMO process right from their desk. The most im­por­tant com­pli­ance pa­ra­me­ters of chain of iden­ti­ty, chain of cus­tody, chain of con­di­tion and lim­it­ed time hori­zon for crit­i­cal­ly ill pa­tients can be mon­i­tored right at one’s fin­ger­tips. Any events, de­lays or changes can be ad­dressed im­me­di­ate­ly. With some up­front ini­tial ef­fort, CD­MOs/CMOs will save a lot of ef­fort down­stream when da­ta is in­te­grat­ed across the en­ter­prise and qual­i­ty and pro­duc­tion teams are re­lieved of an enor­mous doc­u­men­ta­tion bur­den. Com­pa­nies who have adopt­ed EBRs have re­port­ed an 83% de­crease in da­ta in­put er­rors and more than 87% de­crease in re­view time af­ter pro­duc­tion com­pletes by em­brac­ing re­view by ex­cep­tion par­a­digm^4.

To learn more about Dig­i­tal So­lu­tions for Cell and Gene man­u­fac­tur­ing feel free to con­tact me at Rachit.Jain@werum.com.

Down­load our white pa­pers to learn more about this top­ic and un­der­stand how elec­tron­ic batch record­ing has sup­port­ed cell and gene man­u­fac­tur­ers to scale up and be­come suc­cess­ful.

To find out how Werum IT So­lu­tions can help you solve your pre­ci­sion and per­son­al­ized cell and gene man­u­fac­tur­ing chal­lenges be sure to vis­it https://www.werum-amer­i­ca.com/en/it-so­lu­tions/cell-gene/

Bib­li­og­ra­phy

1. https://www.ariz­ton.com/mar­ket-re­ports/cell-and-gene-ther­a­py-mar­ket
2. https://kisacore­search.com/events/octs-2020
3. https://www.gmp-com­pli­ance.org/gmp-news/fda-changes-cgmp-rules-21-cfr-210-211
4. How to Speed up Cell and Gene Ther­a­py

*Com­pa­nies here are syn­ony­mous to uni­ver­si­ties, hos­pi­tals, clin­ics, in­de­pen­dent spon­sors, phar­ma­ceu­ti­cal and biotech com­pa­nies and there­of

About Werum IT So­lu­tions

Werum IT So­lu­tions is the world’s lead­ing phar­ma, biotech and cell and gene ther­a­py elec­tron­ic batch record­ing so­lu­tions provider. Werum pro­vides the best-in-class man­u­fac­tur­ing IT so­lu­tions for the life sci­ences in­dus­try, in­clud­ing the ma­jor­i­ty of the world’s top 30 phar­ma­ceu­ti­cal and bio­phar­ma­ceu­ti­cal com­pa­nies around the globe, and for many re­gion­al and mid-sized en­ter­pris­es. Werum’s dig­i­tal so­lu­tions help boost pro­duc­tion per­for­mance and im­prove qual­i­ty and com­pli­ance – paving the way to op­er­a­tional ex­cel­lence and lean­er man­u­fac­tur­ing.

In cell and gene ther­a­py, Werum PAS-X MES has a 100% mar­ket share with FDA-ap­proved, CAR-T ther­a­py man­u­fac­tur­ers. PAS-X EBR pro­vides out-of-the-box max­i­mum stan­dard func­tion­al­i­ty for all ap­pli­ca­tions in the phar­ma­ceu­ti­cal and bio­phar­ma­ceu­ti­cal sec­tor. Com­pa­nies us­ing PAS-X ben­e­fit from lean pro­duc­tion and op­er­a­tional ex­cel­lence.

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